Kern D E, Klarnet J P, Cheever M A, Greenberg P D
Department of Microbiology/Immunology, University of Washington, Seattle 98195.
Cancer Res. 1990 Oct 1;50(19):6256-63.
Tumors may contain immunogenic antigens that are only recognizable in the context of class I, and not of class II, MHC molecules. Therefore, methods were developed to analyze the capacity of Lyt-2+ T-cells to respond to a syngeneic tumor in the absence of a contribution by L3T4+ T-cells. Conditions were defined in which purified Lyt-2+ T-cell populations, as well as L3T4+ T-cell populations, isolated from immune B6 spleen cells, could be induced to proliferate specifically in response to FBL, a retrovirally induced syngeneic tumor, without the addition of exogenous lymphokines. The purity of the subset responses was documented functionally by selective inhibition of the proliferative response of only the appropriate subset following addition of anti-Kb/Db or anti-I-Ab. The antigen and accessory cell (AC) requirements for triggering immune Lyt-2+ and L3T4+ T-cell populations were examined. The response of L3T4+ populations was predominantly specific for retrovirus envelope gp70, whereas Lyt-2+ populations predominantly recognized tumor antigens other than gp70, consistent with the hypothesis that some tumor antigens may be preferentially recognized by only class I- or class II-restricted T-cells. The FBL-stimulated proliferative response of each T-cell subset was dependent upon the presence of syngeneic AC. However, exogenous interleukin 1 was able to replace AC during the response of Lyt-2+ populations, whereas L3T4+ populations required AC also to biochemically process tumor-derived antigen and present it in the context of class II MHC molecules. The results suggest that under some conditions only the presence of AC or interleukin 1 may be limiting for the induction of antitumor responses by Lyt-2+ populations. These studies analyzed the ability to trigger purified Lyt-2+ T-cells in vitro following in vivo priming to tumor, and it remained possible that L3T4+ T-cells made an essential contribution during in vivo priming. Therefore, L3T4(+)-deficient mice were primed with FBL in vivo, and the Lyt-2+ T-cell response was assessed. Although priming was clearly less efficient in the absence of L3T4+ T-cells, Lyt-2+ T-cells from L3T4(+)-deficient mice proliferated and became cytolytically active following stimulation with FBL. Thus, under appropriate conditions, Lyt-2+ T-cells can generate an effective antitumor response in the absence of L3T4+ T-cells or exogenous lymphokines.
肿瘤可能含有免疫原性抗原，这些抗原仅在I类主要组织相容性复合体（MHC）分子的背景下可被识别，而在II类MHC分子背景下则不然。因此，人们开发了一些方法来分析Lyt-2⁺ T细胞在没有L3T4⁺ T细胞参与的情况下对同基因肿瘤作出反应的能力。确定了一些条件，在这些条件下，从免疫的B6脾细胞中分离出的纯化Lyt-2⁺ T细胞群体以及L3T4⁺ T细胞群体，在不添加外源性淋巴因子的情况下，能够被诱导对FBL（一种逆转录病毒诱导的同基因肿瘤）产生特异性增殖。通过添加抗Kb/Db或抗I-Ab后仅选择性抑制相应亚群的增殖反应，从功能上证明了亚群反应的纯度。研究了触发免疫的Lyt-2⁺和L3T4⁺ T细胞群体所需的抗原和辅助细胞（AC）。L3T4⁺群体的反应主要针对逆转录病毒包膜糖蛋白gp70，而Lyt-2⁺群体主要识别除gp70以外的肿瘤抗原，这与某些肿瘤抗原可能仅被I类或II类限制性T细胞优先识别的假设一致。每个T细胞亚群对FBL刺激的增殖反应依赖于同基因AC的存在。然而，外源性白细胞介素1在Lyt-2⁺群体的反应过程中能够替代AC，而L3T4⁺群体还需要AC对肿瘤衍生抗原进行生化加工，并将其呈递在II类MHC分子的背景下。结果表明，在某些条件下，仅AC或白细胞介素1的存在可能是Lyt-2⁺群体诱导抗肿瘤反应的限制因素。这些研究分析了体内经肿瘤致敏后在体外触发纯化Lyt-2⁺ T细胞的能力，并且L3T4⁺ T细胞在体内致敏过程中仍有可能发挥重要作用。因此，用FBL对L3T4⁺缺陷小鼠进行体内致敏，并评估Lyt-2⁺ T细胞反应。尽管在没有L3T4⁺ T细胞的情况下致敏效率明显较低，但来自L3T4⁺缺陷小鼠的Lyt-2⁺ T细胞在受到FBL刺激后仍能增殖并变得具有细胞溶解活性。因此，在适当条件下，Lyt-2⁺ T细胞在没有L3T4⁺ T细胞或外源性淋巴因子的情况下能够产生有效的抗肿瘤反应。
